Balloon encapsulation and isovolumetric suction thrombectomy catheter and methods thereof

ABSTRACT

The disclosure provides for an adjustable catheter system with isovolumetric suction and restoration of fluid for the removal of a thrombus and a method of use thereof. The catheter system includes an inner catheter and an outer sheath surrounding at least a portion of the inner catheter. The inner catheter may include at least three lumina extending from the proximal end to the distal end of the inner catheter, at least one infusion fenestration along the infusion segment, and a distal encapsulation balloon at the distal end. The outer sheath may include at least three lumina extending from the proximal end to the distal end of the outer sheath and a proximal encapsulation balloon at the distal end. The catheter system may further include an agitator for mechanical morcellation of the thrombus.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.62/842,975, filed May 3, 2019, and U.S. Provisional Application No.62/736,890, filed Sep. 26, 2018, the contents of which are entirelyincorporated by reference herein.

FIELD

The present disclosure is directed to a balloon encapsulation suctionthrombectomy catheter and methods of use thereof.

BACKGROUND

Over the past two decades the incidence and prevalence of deep veinthrombosis (DVTs) and pulmonary embolism (PE) have increased due tohigher use of indwelling central venous catheters (CVCs), inferior venacava (IVC) filters, and venous stent implantations. The most common riskfactors for DVT and/or PE include age, obesity, pregnancy,pharmacological contraception, malignant disease, and immobility. Theetiological factors of DVTs and PEs are found among Virchow's triad ofvenous blood stasis, venous injury, and hypercoagulability. Under thesecircumstances, foci of thrombus can develop and propagate to points ofdecreased venous outflow, i.e. behind valves or at venous branch points,and lead to an organized column of acute thrombus. Incomplete resolutioncan lead to further thrombus propagation, instability, fragmentation,chronic thromboembolic pulmonary hypertension (CTEPH), and venousthromboembolism (VTE). However, even when thrombus is stabilized andpropagation is prevented, the resultant residual obstructive chronic DVTwithin the venous structure can lead to post-thrombotic syndrome (PTS).

The 2016 American College of Chest Physicians (ACCP) recommends forpatients with acute DVT initial treatment with low-molecular weightheparin (LMWH) followed by a course of therapeutic anticoagulation (AC),but it does not produce clot lysis and prevent PTS. Catheter-basedendovascular technology such as catheter-directed thrombolysis (CDT),rheolytic pharmacomechanical thrombectomy, and mechanical suctionthrombectomy each have their advantages and disadvantages for thetreatment of VTE. However, all have limited efficacy in the treatment ofPE.

There are currently no endovascular devices that are specificallydesigned for the treatment of massive (PE causing hemodynamiccompromise) and sub-massive PEs (PE causing cardiac dysfunction).Additionally, recent evidence from various large multicenter randomizedcontrolled trials has questioned the efficacy of CDT endovasculardevices. CDT endovascular devices have been shown to reduce PTS, butultimately did not alter quality of life for patients with proximal DVT.In particular, existing technologies have the following limitations:lack of a clot removal device tailored for the iliocaval venous system,ineffective localized thrombolysis leading to systemic dispersal,ineffective encapsulation of clot during lysis to avoid VTE, andatraumatic thrombectomy to avoid venous wall damage and long-term PTS.

Accordingly, there remains a need for a feasible and translatabletreatment strategy for DVT and massive and sub-massive PEs thatminimizes the risk of VTE and PTS to reduce the high morbidityassociated with this condition.

BRIEF SUMMARY

The disclosure provides for a catheter system for the removal of athrombus. In some embodiments, the catheter system may be used for thetreatment of PE. In an aspect, the catheter system may include an innercatheter having a proximal end, an infusion segment, and a distal end.The inner catheter may include at least one infusion fenestration alongthe infusion segment and a distal encapsulation balloon at the distalend. The catheter system may also include an outer sheath having aproximal end and a distal end. The outer sheath may include a proximalencapsulation balloon at the distal end. The outer sheath surrounds atleast a portion of the inner catheter. In some aspects, the cathetersystem further includes an agitator operable to agitate the thrombus.

In an aspect, the inner catheter further includes at least three luminaextending from the proximal end to the distal end of the inner catheter,for example, an inflation lumen, a guide wire lumen, and an infusionlumen. In an aspect, the infusion segment comprises more than oneinfusion fenestration fluidly connected to the infusion lumen.

In another aspect, the outer sheath may further include at least threelumina extending from the proximal end to the distal end of the outersheath, for example, an inflation lumen, a suction lumen, and a catheterlumen. The inner catheter may be positioned within the catheter lumen.

In an aspect, the agitator includes a plurality of protrusions. Theagitator may advance and retract over the catheter lumen. In anotheraspect, the agitator may be a rotatable wire that extends from thedistal end of the outer sheath. The distal encapsulation balloon and theproximal may form a treatment area. The thrombus to be removed may becontained within the treatment area. The infusion segment is within thetreatment area. In an aspect, the inner catheter further comprises amanifold at its proximal end comprising an infusion port, a ballooninflation port, and a guidewire access port, wherein each port isfluidly connected to one of the at least there lumina of the innercatheter. In another aspect, the outer sheath further comprises amanifold at its proximal end comprising a suction port, a ballooninflation port, and a device access port, wherein each port is fluidlyconnected to one of the at least there lumina of the outer sheath.

Further provided herein is a method of removing a thrombus in a patientin need thereof. In an aspect, the method may include inserting thecatheter system of claim 1 to a treatment area, inflating the distalencapsulation balloon through an inflation lumen of the inner catheter,inflating the proximal encapsulation balloon through an inflation lumenof the outer sheath, mechanically lysing the thrombus with the agitator,infusing an infusion solution to the treatment area through the at leastone infusion fenestration, applying negative suction to the treatmentarea through a suction lumen of the outer sheath, and removing thecatheter system from the patient.

In an aspect, the infusion solution is a thrombolytic solution, saline,or combinations thereof. The thrombolytic solution may include tPA. Inan aspect, the negative suction may be applied for about 2 minutes. Inanother aspect, mechanically lysing the thrombus comprises advancing andretracting the agitator over the catheter lumen. In yet another aspect,mechanically lysing the thrombus may include rotating the agitator. Inan aspect, greater than about 90% luminal patency of the treatment areais restored.

Also provided herein is a method of treating a pulmonary embolism in apatient in need thereof, the method comprising advancing the cathetersystem from a femoral vein cannulation or an internal jugular veincannulation.

Additional embodiments and features are set forth in part in thedescription that follows, and will become apparent to those skilled inthe art upon examination of the specification or may be learned by thepractice of the disclosed subject matter. A further understanding of thenature and advantages of the disclosure may be realized by reference tothe remaining portions of the specification and the drawings, whichforms a part of this disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

The description will be more fully understood with reference to thefollowing figures and data graphs, which are presented as variousembodiments of the disclosure and should not be construed as a completerecitation of the scope of the disclosure, wherein:

FIG. 1 is a perspective view of the catheter system within a vesselrelative to an intraluminal guide wire in one embodiment.

FIG. 2A is a side view of the catheter system deployed intraluminallywith the agitator retracted in one embodiment.

FIG. 2B is a side view of the catheter system deployed intraluminallywith the agitator deployed in the treatment area in one embodiment.

FIG. 3 is side view of the inner catheter that is equipped with aninfusion port, balloon inflation port, and guide wire access port in oneembodiment. The inner catheter is also composed of an infusion segmentwith infusion fenestrations and a distal encapsulation balloon.

FIG. 4A is a cross-sectional view of the inner catheter multi-lumendesign with an infusion lumen, a guide wire lumen, and an inflationlumen in one embodiment.

FIG. 4B is a cross-sectional view of the inner catheter multi-lumendesign with an infusion lumen, a guide wire lumen, and an inflationlumen in one embodiment.

FIG. 4C is a cross-sectional view of the inner catheter multi-lumendesign with an infusion lumen, a guide wire lumen, and an inflationlumen in one embodiment.

FIG. 4D is a cross-sectional view of the inner catheter multi-lumendesign with an infusion lumen, a guide wire lumen, and an inflationlumen in one embodiment.

FIG. 4E is a cross-sectional view of the inner catheter multi-lumendesign with an infusion lumen, a guide wire lumen, and an inflationlumen in one embodiment.

FIG. 4F is a cross-sectional view of the inner catheter multi-lumendesign with an infusion lumen, a guide wire lumen, and an inflationlumen in one embodiment.

FIG. 4G is a cross-sectional view of the inner catheter multi-lumendesign with an infusion lumen, a guide wire lumen, and an inflationlumen in one embodiment.

FIG. 5A is an end view of the infusion segment of the inner catheter.

FIG. 5B is an isometric view of the infusion segment of the innercatheter.

FIG. 6A is a side view of the distal encapsulation balloon of the innercatheter.

FIG. 6B is a cross-sectional view of the distal encapsulation balloon ofthe inner catheter.

FIG. 7 is a side view the outer sheath that includes a sheath body, anagitator, a proximal balloon, and an outer manifold with a suction port,balloon inflation port, and a device access port in one embodiment.

FIG. 8A is a cross-sectional view of the outer sheath multi-lumen designwith an inflation lumen, suction lumen, and catheter lumen in oneembodiment.

FIG. 8B is a cross-sectional view of the outer sheath multi-lumen designwith an inflation lumen, suction lumen, and catheter lumen in oneembodiment.

FIG. 8C is a cross-sectional view of the outer sheath multi-lumen designwith an inflation lumen, suction lumen, and catheter lumen in oneembodiment.

FIG. 9A is a side view of the distal encapsulation balloon of the innercatheter.

FIG. 9B is a cross-sectional view of the distal encapsulation balloon ofthe inner catheter.

FIG. 10 is a side view of the catheter system in a vein withcross-sectional views along the length of the catheter.

FIG. 11 is a side view of a combined manifold for the inner catheter andouter sheath.

FIG. 12A is a side view of an agitator in one embodiment.

FIG. 12B is a cross-sectional view of an agitator in one embodiment.

FIG. 12C is a side view of an agitator in one embodiment.

FIG. 12D is a cross-sectional view of an agitator in one embodiment.

FIG. 12E is a side view of an agitator in one embodiment.

FIG. 12F is a cross-sectional view of an agitator in one embodiment.

FIG. 12G is an isometric view of an agitator in one embodiment.

FIG. 12H is a perspective view of an agitator in one embodiment.

FIG. 12I is a perspective view of an agitator in one embodiment.

FIG. 12J is a side view of an agitator in one embodiment.

FIG. 12K is a perspective view of an agitator in one embodiment.

FIG. 13A is a cross-sectional view of an agitator that is designed toadvance and retract over the outer device sheath inner lumen housing theinner device catheter in one embodiment.

FIG. 13B is a cross-sectional view of an agitator that is designed toadvance and retract over the outer device sheath inner lumen housing theinner device catheter in one embodiment.

FIG. 13C is a perspective view of an agitator in one embodiment.

FIG. 14 is an isometric view of the catheter system on one embodiment.

FIG. 15 is a graph comparing the catheter system to the Indigo® Penumbracatheter showing that the catheter system is able to more efficientlyremove thrombus in a bench-top thrombectomy experiment. *p<0.01

FIG. 16A is a graph of fluent flow simulation drag coefficient atvarious bristle angles. *p<0.01

FIG. 16B is a graph of fluent flow simulation applied force at variousbristle angles. *p<0.01

FIG. 16C shows bench-top testing of 5 degree offset agitator thatdemonstrates drag and retention of clot with a single passage of theagitator into clot.

DETAILED DESCRIPTION

The disclosure may be understood by reference to the following detaileddescription, taken in conjunction with the drawings as described below.It is noted that, for purposes of illustrative clarity, certain elementsin various drawings may not be drawn to scale.

CDT and PCDT have ineffective localized thrombolysis, leading tosystemic bleeding side effects. Another major limitation of CDT and PCDTcompared to AC alone is the 1.5-fold increase risk of PE and 2-foldincreased need for an adjunct IVC filter placement to avoid thrombusembolization during treatment. Therefore, CDT and PCDT have ineffectiveencapsulation of the treatment zone to avoid dangerousthromboembolization during procedures. Mechanical suction thrombectomyaims to reduce the risk of PE. However, current suction thrombectomydevices have non-suitable calibers and lack proven efficacy fortreatment of DVT. The balloon encapsulation and isovolumetric suctionthrombectomy catheter provided herein overcomes all the major gaps inthe current endovascular thrombectomy devices for the treatment of‘large-volume’ ilio-caval DVT and massive and sub-massive PEs.Therefore, the balloon encapsulation suction thrombectomy catheter maybe used for the efficient removal of venous clots from the pulmonaryartery, vena cava, and iliac veins.

Disclosed herein are balloon encapsulation suction thrombectomy cathetersystems and methods for treatment of massive and sub-massive PEs, IVCand iliac vein DVT. In an embodiment, catheter system provides aminimally invasive solution for efficient and complete removal of a‘large-volume’ thrombus from pulmonary arteries. The catheter system mayinclude chemical, mechanical, and/or suction features for maximalthrombectomy efficiency. In an embodiment, the catheter system may beless invasive than existing procedures and devices. For example, a10-20Fr catheter system, delivered percutaneously, with isovolumetericinfusion and thrombus suction may provide for less invasive manipulationof pulmonary arteries. The catheter system may reduce the operative riskto the patient by maintaining vessel integrity.

In an embodiment, the catheter system may have proximal and distalballoons for encapsulation of a thrombus in a treatment area. In someexamples, the proximal and distal thrombus balloons encapsulation of thethrombus may reduce or prevent distal embolization. The distance betweenthe proximal and distal balloons may be adjustable, thus forming anadjustable treatment area that can be used to accommodate a wide rangeof venous treatment lengths. In another embodiment, the catheter systemmay perform localized isovolumetric suction thrombectomy. The cathetersystem may provide localized catheter-directed thrombolysis in thetreatment zone, which may reduce the risk of bleeding. The cathetersystem may also provide localized mechanical thrombolysis using anagitator. In yet another embodiment, the catheter system may providemechanical agitation of the thrombus with an agitator to facilitateremoval through the isovolumetric suction and restoration of fluid inthe treatment area.

In an embodiment, the agitator and suction features of the cathetersystem may facilitate complete thrombectomy. In some embodiments, thecatheter system may facilitate at least 90%, at least 95%, at least 98%,at least 99%, or at least 100% thrombus removal.

In an embodiment, the catheter system may minimize the length anduncertainty of surgery time. In some embodiments, the length of surgeryusing the catheter system may be up to 30 minutes, up to 45 minutes, upto 1 hour, or up to 2 hours. In various embodiments, the catheter systemmay be used in multiple vessels throughout the body, including, but notlimited to the pulmonary artery, vena cava, iliac veins, femoral vein,right atrium, jugular vein, and/or popliteal vein.

Catheter System

In some examples, the catheter system includes an inner catheter, anouter sheath, and/or an agitator. The inner catheter has a proximal end,an infusion segment, and a distal end. The inner catheter further has atleast one infusion fenestration along the infusion segment and a distalencapsulation balloon at the distal end. The outer sheath has a proximalend and a distal end. The outer sheath further includes a proximalencapsulation balloon at the distal end. In some examples, the outersheath surrounds at least a portion of the inner catheter and the distalencapsulation balloon and the proximal encapsulation balloon areseparated by a distance along the infusion segment.

FIG. 1 shows the distal end of the catheter system 100 relative to anintraluminal guide wire 112. The catheter system 100 includes an innercatheter 101, a distal balloon 104, an outer sheath 106, a proximalballoon 108, and an agitator 110. FIG. 2A is a side view of the cathetersystem 100 within a vessel with the proximal balloon 108 and the distalballoon 104 deployed, creating a treatment area with the infusionsegment 102, and the agitator retracted within the outer sheath 106.FIG. 2B is a side view of the catheter system 100 within a vessel withthe proximal balloon 108 and the distal balloon 104 deployed, creating atreatment area with the infusion segment 102, and the agitator 110deployed intraluminally.

FIG. 3 illustrates the inner catheter 101 having a manifold 114, adistal encapsulation balloon 104, and an infusion segment 102 withinfusion fenestrations 116. The manifold 114 includes an infusion port115, balloon inflation port 117, and guide wire access port 119. FIGS.4A-4G are optional cross-sectional views of the inner catheter 101multi-lumen design with an infusion lumen 103, a guide wire lumen 105,and an inflation lumen 107. FIGS. 5A and 5B illustrate the infusionsegment 102 of the inner catheter 101 with a staggered arrangement ofthe infusion fenestrations 116.

FIG. 7 illustrates the outer sheath 106 that includes an outer manifold118, a sheath body 120, an agitator 110, and a proximal balloon 108. Theouter manifold 118 may include a suction port 121, balloon inflationport 123, and a device access port 125. FIG. 8A-8C are cross-sectionalviews of the outer sheath 106 multi-lumen design with an inflation lumen109, suction lumen 111, and catheter lumen 113. FIGS. 3A-3G are examplesof the agitator 110 that advance and retract over the outer sheath innerlumen housing the inner catheter. FIG. 10 illustrates the cathetersystem within a vessel and provides cross-sections of the inner catheterand outer sheath at various points along the catheter system.

In some examples, the manifold 114 for the inner catheter and the outermanifold 118 for the outer sheath may be connected together to form onecombined manifold, as seen in FIG. 11. The various ports may be operatedas follows. The guidewire is advanced through the guidewire port throughthe thrombus ahead of the catheter system. With all ports sealed, thecatheter system is moved into position proximal to the thrombus. Theproximal balloon inflation port 123 is opened and the proximalencapsulation balloon 108 is inflated. The proximal balloon inflationport 123 is then closed. A Tuohy Valve sealing the inner catheter isreleased, and the inner catheter is advanced distal to the thrombus (4cm of treatment zone length). The inner catheter Tuohy Valve is thensealed. The distal balloon inflation port 117 valve is opened and thedistal balloon 104 is inflated. The distal balloon inflation valve isthen closed.

The order of the following operations may be based upon the discretionof the operator, with the option to mechanically and/or chemicallyagitate the thrombus made available. The infusion port 115 and suctionport 121 valves may be opened, and lytics may be infused through theinfusion port 115 while the same quantity of fluid may be removed viathe suction port 121 to maintain isovolumetric conditions within thetreatment area. The suction and infusion ports 121, 115 may both beclosed, and the mechanical agitator 110 may be moved along the treatmentarea through the device access port 125. In some examples, the deviceaccess port may be a push-rod Tuohy Valve.

Based on the discretion of the operator, these steps may be repeated anynumber of times, possibly with the infusion of saline solution throughthe infusion ports to ensure no lytics remain in the patient followingremoval of the catheter system. The distal balloon inflation port 117 isopened, and the distal balloon 104 is deflated. The distal ballooninflation port 117 is then closed. The Tuohy Valve at the device accessport 125 is opened, and the inner catheter 101 is retracted into theouter sheath 106. The Tuohy Valve is then closed. The proximal ballooninflation port 123 is opened, the proximal balloon 108 is deflated, andthe proximal balloon inflation port 123 is closed. The catheter systemis retracted along the guidewire and removed from the patient. Theguidewire is then removed, completing the procedure.

The catheter system can be operated percutaneously and introducedintravenously using the Seldinger technique (a method of introducingcatheters and catheter-based devices into vessels from outside of thebody over a wire). In an embodiment, the catheter system may be flexibleto facilitate advancement from either a femoral vein cannulation orinternal jugular vein cannulation.

Micro- and macro-emboli during venous thrombectomy procedures can beespecially dangerous and can lead to fatal PE. The use of a typicalthrombectomy device has been shown to create upwards of 300,000particles sized 10-100 μm, ˜1,000 particles sized 100-1,000 μm, and ˜20particles larger than 1 mm. In an embodiment, the catheter systemproximal and distal balloon encapsulation design minimizes thrombusparticle embolization.

As seen in FIGS. 1, 2A, and 2B, the catheter system has a tandem balloonencapsulation design with proximal and distal encapsulation balloonsthat conform around the intraluminal thrombus. This adjustable dualballoon design maintains cradling and entrapment of the intraluminalthrombus to reduce the risk of intra-procedural thrombus embolization,facilitate corralling of the thrombus into the proximal suction port ofthe device, reduce the risk of imprecise treatment of specific venoussegments and systemic leakage of thrombolytic agents, and minimizetrauma to the vessel wall.

The adjustability of the distance between the proximal and distalencapsulation balloons allows for adjustability of the thrombolytictreatment area between the balloons. In some examples, the distancebetween the proximal and distal encapsulation balloons is determinedbased on how far the inner catheter is permitted to extend beyond theouter sheath. The treatment area is then set by the inflation of boththe proximal and distal encapsulation balloons. This also locks thecatheter system in place within the vessel. In various examples, thetreatment area length may range from about 1 cm to about 25 cm. In oneexample, the treatment area may have a length of about 4 cm. Thethrombus to be removed is contained within the thrombolytic treatmentarea. In addition, the infusion segment of the inner catheter is withinthe thrombolytic treatment area. The variable length of the treatmentarea allows for the accommodation of a range of dot geometries andprovides freedom to treat a clot in a staged fashion.

The catheter system may further facilitate release of a fluid throughthe infusion segment of the inner catheter. In some examples, the fluidmay contain thrombolytics and/or contrast agents. In an embodiment, thethrombolytics may be infused through infusion fenestrations in aninfusion segment of the inner catheter of the catheter system.

The inner catheter and outer sheath are operable to provideisovolumetric suction and restoration of fluid within the thrombolytictreatment area. For example, the catheter system further utilizesisovolumetric aspiration for the removal of the thrombus from thetreatment area. The catheter system includes both an inner catheterinfusion port (FIG. 3) and an outer sheath negative suction port (FIG.7) to allow movement of fluid into and out of the treatment area. Theinner catheter infusion port is intended to facilitate both thrombolyticmedication administration as well as provide an inflow saline circuit toprevent venous wall collapse during outer sheath negative suction. In anembodiment, the inner catheter may be used as both a thrombolyticinfusion catheter as well as a saline infusion port to facilitateisovolumetric thrombus aspiration from the venous treatment area. Theouter sheath suction port may have a large aspiration lumen to rapidlyevacuate clot fragments and accommodate a range of negative suctionstrengths.

The catheter system further includes an agitator, such as bristlemorcellation to mechanically agitate the thrombus. The built-inagitator/morcellation design may enhance the catheter system'sefficiency in thrombus fragmentation and evacuation. The agitator may beused for thrombus engagement, thrombus fragmentation, and pulling thethrombus into the mechanical suction thrombectomy port. The clotagitation may avoid contact, and thus damage to the vessel wall.

Inner Catheter

The catheter system 100 includes an inner catheter 101. The innercatheter has a proximal end, an infusion segment, and a distal end. Inan embodiment, the inner catheter includes at least three lumina, atleast one infusion fenestration along the infusion segment, and a distalencapsulation balloon at the distal end of the inner catheter. The innercatheter may further include a manifold at its proximal end comprisingan infusion port, a balloon inflation port, and a guidewire access port,such that each port is fluidly connected to one of the at least therelumina of the inner catheter.

As seen in FIGS. 4A-4G, the at least three lumina of inner catheter mayinclude, but are not limited to an inflation lumen 107, a guidewirelumen 105, and an infusion lumen 103. These lumina extend from theproximal end to the distal end of the inner catheter and are eachfluidly connected to one of the ports at the proximal end of the innercatheter. For example, the inflation lumen is fluidly connected to theballoon inflation port, the guidewire lumen is fluidly connected to theguidewire access port, and the infusion lumen is fluidly connected tothe infusion port. In some examples, manifold with the balloon inflationport, the guidewire access port, and the infusion port may be combinedwith the outer manifold of the outer sheath, as shown in FIG. 11.

FIGS. 4A-4G show example cross sections of the inner catheter. Ingeneral, the infusion lumen is the largest of the three lumina in theinner catheter. In some examples, the inner catheter includes a large“D-shaped” infusion lumen and twin lumina beneath it for the guide wireand distal balloon inflation. The guide wire may exit the inner catheteralong the centerline and may be the only lumen past the distal balloon.

The inner catheter may have an outer diameter of about 4 French to about7 French. In one embodiment, the inner catheter has an outer diameter ofabout 5.5 French. The inner catheter may have a length ranging fromabout 60 cm to about 160 cm. In one embodiment, the inner catheter has alength of about 100 cm from the distal edge of the manifold to thedistal end of the distal encapsulation balloon.

The infusion segment 102 of the inner catheter 101 includes at least onefenestration 116 which is fluidly connected to the infusion lumen toenable infusion of a fluid into the treatment area. In some examples,the fluid is an infusion solution. In an embodiment, an infusionsolution that is introduced in the infusion port will travel through theinfusion lumen and exit the inner catheter at the at least onefenestration. In some embodiments, the infusion solution is athrombolytic solution, saline, or combinations thereof. In anembodiment, the infusion solution may be introduced into the inflationport with a syringe.

In an embodiment, the infusion fenestrations have a diameter of about0.01 inches to about 0.5 inches. In one example, the fenestrations havea diameter of about 0.02 inches. In some examples, the fenestrationshave a diameter of less than 0.5 mm. In another example, thefenestrations have a diameter of about 0.4 mm. The number of infusionfenestrations along the length of the infusion segment may vary fromabout 1 to about 5 fenestrations per cm of the infusion segment. In someexamples, the fenestrations may be spaced about 2 mm apart. In oneexample, treatment area of about 4 cm with 0.4 mm diameter fenestrationsspaced 2 mm apart in a staggered formation would result in 21 totalfenestrations.

The fenestrations may be in a staggered formation or may be in anordered formation. The infusion segment may include infusionfenestrations along the right, top, and left planes of the innercatheter. In an example, the infusion fenestrations are separated fromone another along each plane equidistant from one another, and arestaggered across the three planes by beginning their spacing patternslightly further on each plane.

In an embodiment, lytics may be infused into a 4 cm-long treatment areaalong three lines of 0.4 mm outer diameter infusion fenestrationsoriented along the top, right, and left planes of the infusion segmentof the inner catheter. Along each of the three lines, each fenestrationmay be separated along its centerline by about 6 mm, while eachfenestration may be separated from its counterpart on the adjacent planeby about 2 mm. For example, a fenestration may be present on the rightplane, and on the top plane about 2 mm away along the inner catheter'slength. This allows for infusion to occur along three planes whilemaintaining the structural integrity of the inner catheter. Thesefenestrations run the length of infusion segment in the treatment area,which in concert with the suction lumen in the outer sheath help tomaintain isovolumetric conditions by regulating fluid volume in thewhole of the treatment area.

The guidewire lumen is configured to receive a guidewire such that thecatheter system may be inserted into a patient using standard catheterintroducing techniques. In various embodiments, the guidewire lumen hasa diameter of about 0.02 inches to about 0.1 inches. In one embodiment,the guidewire lumen has a diameter of about 0.038 inches. In an example,as seen in FIGS. 4A-B and 4E-4G, the guidewire lumen 105 may beconcentric with or centrally located within the inner catheter 101. Inother examples, the guidewire lumen 105 may be off-center within theinner catheter 101.

The inflation lumen 107 may be fluidly connected to the distalencapsulation balloon 104 at the distal end of the inner catheter. Forexample, a fluid may be introduced through the inflation port, travelthrough the inflation lumen, and inflate the distal encapsulationballoon. In some embodiments, the fluid may be saline, a biocompatiblefluid, atmospheric air, and/or pressurized air. In an embodiment, thefluid may be introduced into the inflation port with a syringe.

The distal encapsulation balloon may have an average diameter of about 5mm to about 30 mm. In one embodiment, the distal encapsulation balloonhas a diameter of about 15 mm. The distal encapsulation balloon may havea cylindrical, conical, oval, or circular shape. For example, the distalencapsulation balloon 104 may have a substantially cylindrical shapewith tapered ends, as seen in FIGS. 6A and 6B. In some aspects, thedistal encapsulation balloon may have a combination of shapes. Forexample, as seen in FIG. 3, the proximal portion of the distalencapsulation balloon may be substantially cylindrical in shape and thedistal portion of the distal encapsulation balloon may have a tapered orconical shape. In various embodiments, the distal encapsulation balloonmay have a length of about 1 cm to about 5 cm. In one embodiment, thedistal encapsulation balloon may have a total length of about 1.5 cm. Inan embodiment, the proximal end of the distal encapsulation balloon maybe concave. The distal encapsulation balloon may have a proximalconcavity of about 5° to about 15°. In one embodiment, the distalencapsulation balloon may have a concavity of about 10°.

The distal encapsulation balloon may be a compliant balloon operable toaccommodate varying vessel sizes and minimize damage or injury to thevessel. The distal encapsulation balloon may be made of polyethyleneterephthalate (PET), polyurethane, or any other biocompatible polymercapable of expanding to the appropriate diameters.

Outer Sheath

The catheter system 100 further includes an outer sheath 106 with aproximal encapsulation balloon 108, as seen in FIG. 7. The outer sheathhas a proximal end and a distal end. In an embodiment, the outer sheathincludes at least three lumina extending from the proximal end to thedistal end of the outer sheath, and a proximal encapsulation balloon 108at the distal end. The outer sheath further includes a manifold 118 atits proximal end with a suction port 121, a balloon inflation port 123,and a device access port 125, such that each port is fluidly connectedto one of the at least there lumina of the outer sheath. The outersheath may have a roughly “power symbol” design, with consistent wallthicknesses to ensure structural stability and a larger lumen for theballoon in the “rail” riding along the length of the outer sheath.

As seen in FIGS. 8A-8C, the outer sheath may include an inflation lumen109, a suction lumen 111, and a catheter lumen 113. These lumina extendfrom the proximal end to the distal end of the outer sheath and are eachfluidly connected to one of the ports at the proximal end of the outersheath. For example, the inflation lumen is fluidly connected to theballoon inflation port, the suction lumen is fluidly connected to thesuction port, and the catheter lumen is fluidly connected to the deviceaccess port.

The outer sheath may have an outer diameter of about 10 French to about26 French. In one embodiment, the outer sheath has an outer diameter ofabout 20 French. In another embodiment, the outer sheath may have aninner diameter of about 18 French. The outer sheath may have a lengthranging from about 50 cm to about 150 cm. In one embodiment, the outersheath has a length of about 65 cm from the distal edge of the manifoldto the distal end of the proximal encapsulation balloon. In someembodiments, the outer sheath has a length that is shorter than theinner catheter. For example, only a portion of the inner catheter iscovered by the outer sheath. This allows for the distal encapsulationballoon on the inner catheter and the proximal encapsulation balloon onthe outer sheath to surround a thrombus within a treatment area.

The catheter lumen is configured to receive the inner catheter such thatthe at least a portion of the inner catheter is surrounded by the outersheath. In this embodiment, the proximal portion of the inner catheter,before the infusion segment, is covered by the outer sheath. In variousembodiments, the catheter lumen has a diameter of about 4 French toabout 22 French. In one embodiment, the catheter lumen has an innerdiameter of about 5.5 French. The catheter lumen may have an outerdiameter of about 7.5 French. In an embodiment, as seen in FIGS. 8A-8C,the catheter lumen may be concentric with or centrally located withinthe outer diameter of the outer sheath. The inner catheter may beinserted into the catheter lumen at the device access port.

The inflation lumen may be fluidly connected to the proximalencapsulation balloon at the distal end of the outer sheath. Forexample, a fluid may be introduced through the inflation port, travelthrough the inflation lumen, and inflate the proximal encapsulationballoon. In some embodiments, the fluid may be saline, a biocompatiblefluid, atmospheric air, or pressurized air. In an embodiment, the fluidmay be introduced into the inflation port with a syringe. In variousembodiments, the inflation lumen may have a diameter of about 1 Frenchto about 4 French. In one embodiment, the inflation lumen has a diameterof about 2 French.

The proximal encapsulation balloon may have an average diameter of about10 mm to about 30 mm. In one embodiment, the proximal encapsulationballoon has a diameter of about 15 mm. The proximal encapsulationballoon may have a cylindrical, conical, oval, or circular shape. Insome aspects, the proximal encapsulation balloon may have a combinationof shapes. For example, as seen in FIGS. 9A and 9B, the distal portionof the proximal encapsulation balloon 108 may be cylindrical in shapeand the proximal portion of the proximal encapsulation balloon may havea tapered or conical shape. In various embodiments, the proximalencapsulation balloon may have a length of about 1 cm to about 3 cm. Inone embodiment, the proximal encapsulation balloon may have a totallength of about 1.5 cm. In an embodiment, the distal end of the proximalencapsulation balloon may be concave. The distal encapsulation balloonmay have a proximal concavity of about 5° to about 15°. In oneembodiment, the distal encapsulation balloon may have a proximalconcavity of about 10°. The proximal encapsulation balloon may be madeof polyethylene terephthalate (PET), polyurethane, or any otherbiocompatible polymer capable of expanding to the appropriate diameters.

The suction lumen may surround the catheter lumen. In variousembodiments, the suction lumen may have a diameter of about 11 French toabout 22 French. In one embodiment, the suction lumen has a diameter ofabout 18 French. The suction lumen is fluidly connected to the suctionport such that a negative suction can be applied to the suction port anddraw up material in the treatment area at the opening of the suctionlumen at the distal end of the outer sheath. In various embodiments, thesuction applied may range from about 0 kPa to about 150 kPa. In someexamples, the suction applied may range from about 0 kPa to about 15kPa. The suction applied through the suction lumen is balanced with theinfusion of the infusion solution through the infusion fenestrations.

Agitator

The catheter system may provide localized mechanical thrombolysis usingan agitator operable to agitate or morcellate the thrombus. Morcellationcan be used to locally fragment the thrombus. The agitator may be usedto mechanically break apart a large thrombus to allow it to be eithersuctioned through the suction lumen or contained between the proximaland distal encapsulation balloons as the catheter system is removed fromthe patient.

As seen in FIGS. 1 and 2B, the agitator may extend from the distal endof the outer sheath and into the treatment area to morcellate thethrombus. In some embodiments, the outer sheath encloses the agitator.In an embodiment, the agitator advances and retracts over the catheterlumen of the outer sheath. For example, the agitator may be rail mountedon the outside of the catheter lumen and the inner catheter to maintainits movement along the centerline of the vasculature. In this example,the agitator may be within the suction lumen when retracted within theouter sleeve. In some examples, the agitator is operable to be usedwithout touching a wall of the vessel. FIGS. 13A-13E show end views orcross-sections of various agitators 110 rail mounted on the outerdiameter of the catheter lumen 113 of the outer sheath, such that it isinside the suction lumen 111 when retracted.

In an embodiment, the agitator may include a plurality of radiallyextending protrusions from a central ring. The protrusions may be fins,bristles, rod-like, cylindrical, rectangular, or curved. In oneembodiment, as seen in FIGS. 12A-12K, the agitator protrusions may befins, rod-like, or cylindrical. The protrusions may be distributedhelically along the length of the agitator. In an embodiment, thecentral ring is a partial ring and partially surrounds the catheterlumen to enable the rail mounting of the agitator. In some examples, theprotrusions are located at the distal end of the central ring and thecentral ring extends a length along the outer sheath to enable actuationor deployment of the actuator, as seen in FIG. 14. In some examples, theagitator may have a length of at least about 15 cm.

The protrusions may have a radially extending length of about 1 mm toabout 5 mm. In some examples, the protrusions may be at a pitch angleoperable to reduce shear stress on the vessel. The pitch angle may rangefrom about 5 degrees to about 65 degrees. In one example, the pitchangle may be about 30 degrees. In another example, the pitch angle maybe about 15 degrees. In an embodiment, the protrusion density and anglecan be optimized to enhance the mechanical traction that the protrusionsapply to the thrombus so as to enhance its morcellation.

In some examples, the protrusions may be fins extending along a lengthof the central ring, as seen in FIGS. 12A-12G. In some examples, thefins may be tapered towards the distal end of the agitator or have acone-like appearance, as seen in FIGS. 12C-12F. Agitator fins may be 5,10, 15, 20, 25, 30, or 90 degrees relative to the central curve of thelongitudinal axis. For example, FIGS. 12A-120 show fins with 0 degreepitch angle and FIGS. 12E-12F show fins with a 30 degree pitch angle. Insome examples, the fins may be rolled to have a semi-helical orientationalong a length of the central ring, as seen in FIGS. 12H-12I. Inadditional examples, rod-like protrusions may be staggered along alength of the central ring, as seen in FIG. 12J. The agitator mayinclude variations of the finned (bolt) design, and may be backed with areinforcing region of similar material. This region may include a“strain release” section in order to allow the agitator to be on therail within the outer sheath even when fully extended into the treatmentarea, while also allowing for flexibility in the catheter which may beimpeded by a solid agitator of a length of 15 cm or more.

In one example, the mechanical agitator is composed of seven fins, each0.4 mm in width and 1 mm in height radiating out from a central ring.The finned portion of the agitator may be 1 cm in length, and the frontface of each fin may be angled at 20 degrees. Each fin is also “rolled”from the centerline of the agitator at 5 degrees, the combination ofthese angles having been found to better engage thrombus. The agitatormay be connected to the inner catheter which runs along the catheterlumen of the outer sheath by three wires, connected on the left, right,and bottom planes of the agitator. This allows for flexibility in theoverall catheter system, as the agitator is able to ride along bendsmade in the catheter.

In another embodiment, the agitator is at least one protrusion or rodextending into the treatment area. For example, the agitator may be asingle, curved rod or wire, as seen in FIG. 12K. For example, a cleanerwire may be advanced through the device access port. In this embodiment,the catheter system may only include an outer sheath or catheter, aproximal balloon, and the cleaner wire.

Methods of Thrombus Removal

Provided herein are methods of treatment using the catheter system. Inan embodiment, the catheter system is used to treat PE. For example, thecatheter system may be advanced from a femoral vein cannulation orinternal jugular vein cannulation. The catheter system may then bedeployed by inflating the encapsulation balloons, agitating thethrombus, and using isovolumetric suction and restoration of fluid toremove the thrombus.

Further provided herein is a method of removing a thrombus in a patientin need thereof. The method may include inserting the catheter systeminto a treatment area containing the thrombus. The distal encapsulationballoon may then be inflated through an inflation lumen of the innercatheter and the proximal encapsulation balloon may then be inflatedthrough an inflation lumen of the outer sheath. The inflated distal andproximal encapsulation balloons are inflated such that they encapsulateor surround the thrombus to be removed.

To aid in removal of the thrombus, the method may include localizedmechanical thrombolysis using an agitator. Morcellation can be used tolocally fragment the thrombus. This may include mechanically moving theagitator in, out, and/or around the treatment area to break apart thethrombus. In one embodiment, morcellating includes advancing andretracting the agitator over the catheter lumen such that theprotrusions of the agitator are moved within the treatment area. Thecatheter system's agitator can be advanced into the thrombosed segmentin a controlled fashion.

The method may further include applying isovolumetric suction andrestoration of fluid to the treatment area. Localized negative suctionmay be applied to the treatment area through a suction lumen of theouter sheath. The negative suction may provide for removing at least aportion of the thrombus through the suction lumen. The negative suctionmay also allow for retaining the thrombus within the treatment area,i.e. between the encapsulation balloons. The suction port may beattached to a negative suction pump capable of delivering a pure vacuumof about 5-40 inHg or about 17-135 kPa. The negative suction pump may beattached to a reservoir canister/bag to collect thrombus. In oneembodiment, the reservoir canister/bag may be 1,000 mL.

In various embodiments, the negative suction may be applied for lessthan about 30 seconds, about 30 seconds, about 1 minute, about 2minutes, about 5 minutes, or more than 5 minutes. In one embodiment, thenegative suction is applied for about 2 minutes. To counter the negativesuction within the treatment area, the method may also include infusingan infusion solution to the treatment area through the at least oneinfusion fenestration. The infusion solution may be a thrombolyticsolution, saline, or combinations thereof. The infusion solution mayalso work in combination with the agitator to break apart the thrombusfor removal.

The method may optionally include infusing a thrombolytic through theinner catheter for localized chemical thrombolysis. The infusionfenestrations in the inner catheter may facilitate release of thethrombolytics at the infusion segment or distal end of the innercatheter. In one embodiment, the thrombolytic may be tissue plasmogenactivator (tPA). The concentration of thrombolytic may range from about1 mg/mL to about 40 mg/m L. In various embodiments, the thrombolyticconcentration released by the catheter system may be about 1 mg/mL,about 5 mg/mL, about 10 mg/mL, about 20 mg/mL, about 30 mg/mL, or about40 mg/mL. For example, the tPA concentration may be about 5-20 mg inabout 20-200 mL.

The method may further include removing the catheter system from thepatient. When the catheter system is removed, the proximal and distalencapsulation balloons may remain inflated such that any remainingportion of the thrombus remains encapsulated between the balloons as thesystem is removed from the patient. In various embodiments, greater thanabout 80% luminal patency is restored, greater than about 85% luminalpatency is restored, greater than about 90% luminal patency is restored,greater than about 95% luminal patency is restored, or greater thanabout 99% luminal patency is restored after removal of the thrombus withthe catheter system. In an embodiment, greater than about 90% luminalpatency of the treatment area is restored.

In other embodiments, a catheter system including an outersheath/catheter, proximal balloon, and agitator may be utilized. In thisembodiment, the outer catheter may be advanced proximal to the thrombus.The proximal balloon may then be inflated to allow for proximal fixationand halting of PA inflow. The agitator (e.g. cleaner wire) may then beadvanced through the device access port. Then, negative retrogradesuction may be initiated as the cleaner wire is rotated to beginthrombus fragmentation.

In an embodiment, the catheter system provides a minimally invasive andefficient removal of ‘large-volume’ thrombus from the ilio-caval venoussegment. In some embodiments, the catheter system provides at leastabout 90%, at least about 95%, at least about 98%, at least about 99%,or near 100% retrieval of an intravenous thrombus. In an embodiment, thecatheter system may minimize the risk of trauma to the venous lumen andendothelium. The catheter system may also have compatibility withexisting catheter-based platforms and technology. In an embodiment, thecatheter system has the ability to effectively fragment and evacuate anintraluminal thrombus. For example, the Examples below show the cathetersystem design is superior to the Indigo® catheter in engaging a thrombusand evacuating it (FIG. 15).

EXAMPLES Example 1: Preliminary Comparative Analysis of PrototypeSuction Thrombectomy Efficiency

A balloon encapsulation endovascular thrombectomy catheter system(referred to herein as Hydra) was tested using the methods in theExamples below. Custom-morph polyethylene terephthalate (PET) balloonswere developed. A bench-top IVC luminal thrombus model was developed forinitial comparative testing between the Hydra catheter and Indigo®Penumbra catheter. 5 cm³ of subacute thrombus was engaged with 70 kPAnegative suction using the Hydra catheter and Indigo® Penumbra catheter.Over the course of 1 minute the Hydra catheter was able to moreefficiently remove the thrombus (p<0.01; FIG. 15).

Example 2: Agitator Analysis

To test some designs of the agitator and agitator fins, as seen in FIGS.12A-12F, were varied at 5, 10, 15, and 30 degrees relative to thelongitudinal axis of the agitator. Each variation of the agitator wasanalyzed using a flow simulation with all other variables held constant.The force applied by the forward face of the agitator was determined andused to calculate C_(d) of each fin angle design. FIG. 16A providesresults of the calculated drag coefficient for various fin angleoffsets. FIG. 16B provides results of the calculated applied force forvarious fin angle offsets. In general, drag coefficient and appliedforce were highest at 5 degrees bristle off-set angle. Bench-top testingof 5 degree offset agitator demonstrated drag and retention of clot witha single passage of the agitator into the clot, as seen in FIG. 16C.

To test some designs of the agitator and agitator fins, as seen in FIGS.12H and 12I, agitator fin angles were varied at 5, 10, 15, 20, 25, 30,and 90 degrees relative to the central curve of the longitudinal axis.Each variation of the agitator was analyzed using a flow simulation withall other variables held constant. The force F required to hold theagitator in place as a viscous fluid passed across it at a flow rate ofv was determined and used to calculate and effective drag coefficientC_(d) of each fin angle design, where C_(d)=2 F/((v{circumflex over( )}2)ρA), in which ρ is the fluid density and A is sum of thecross-sectional areas of each agitator and its fins. Table 1 providesresults of the calculated drag coefficient for various fin angleoffsets, and shows that fin angle acuity affects the drag coefficient.

TABLE 1 Applied Force, F Cross- Fin [N] to Hold sectional Drag angleHydra Agitator Area, A Coefficient (degrees) (Averaged Value)[m{circumflex over ( )}2] (C_(d)) 90 4.57E−06 3.12E−05 30.1 5 3.98E−052.68E−05 306 10 3.79E−05 2.67E−05 292 15 2.19E−05 2.66E−05 169 201.24E−05 2.64E−05 97.0 25 2.46E−05 2.63E−05 193 30 1.12E−05 2.61E−0588.3

Having described several embodiments, it will be recognized by thoseskilled in the art that various modifications, alternativeconstructions, and equivalents may be used without departing from thespirit of the invention. Additionally, a number of well-known processesand elements have not been described in order to avoid unnecessarilyobscuring the present invention. Accordingly, the above descriptionshould not be taken as limiting the scope of the invention.

Those skilled in the art will appreciate that the presently disclosedembodiments teach by way of example and not by limitation. Therefore,the matter contained in the above description or shown in theaccompanying drawings should be interpreted as illustrative and not in alimiting sense. The following claims are intended to cover all genericand specific features described herein, as well as all statements of thescope of the present method and system, which, as a matter of language,might be said to fall therebetween.

Numerous examples are provided herein to enhance the understanding ofthe present disclosure. A specific set of statements are provided asfollows.

Statement 1: A catheter system for removal of a thrombus from a vessel,comprising: an inner catheter having a proximal end, an infusionsegment, and a distal end, the inner catheter comprising: at least oneinfusion fenestration along the infusion segment; and a distalencapsulation balloon at the distal end; and an outer sheath having aproximal end and a distal end, the outer sheath comprising: a proximalencapsulation balloon at the distal end, wherein the outer sheathsurrounds at least a portion of the inner catheter and the distalencapsulation balloon and the proximal encapsulation balloon areseparated by a distance along the infusion segment.

Statement 2: The catheter system of Statement 1, wherein the distalencapsulation balloon and the proximal encapsulation balloon arecompliant balloons operable to accommodate varying vessel sizes andminimize damage or injury to the vessel.

Statement 3: The catheter system of Statement 1, wherein the distancebetween the distal encapsulation balloon and the proximal encapsulationballoon is adjustable.

Statement 4: The catheter system of Statement 1, wherein the distancebetween the distal encapsulation balloon and the proximal encapsulationballoon form a thrombolytic treatment area, wherein the thrombus to beremoved is contained within the thrombolytic treatment area.

Statement 5: The catheter system of Statement 4, wherein the infusionsegment is within the thrombolytic treatment area.

Statement 6: The catheter system of Statement 5, wherein the innercatheter is operable to infuse a fluid to the thrombolytic treatmentarea and the outer sheath is operable to provide suction to remove fluidfrom the thrombolytic treatment area.

Statement 7: The catheter system of Statement 6, wherein the innercatheter and outer sheath are operable to provide isovolumetric suctionand restoration of fluid within the thrombolytic treatment area.

Statement 8: The catheter system of Statement 1, wherein the innercatheter further comprises at least three lumina extending from theproximal end to the distal end of the inner catheter.

Statement 9: The catheter system of Statement 8, wherein the innercatheter comprises an inflation lumen, a guide wire lumen, and aninfusion lumen, and wherein the at least one infusion fenestration alongthe infusion segment is connected to the infusion lumen to enableinfusion of fluid.

Statement 10: The catheter system of Statement 9, wherein the innercatheter further comprises a manifold at its proximal end comprising aninfusion port, a balloon inflation port, and a guidewire access port,wherein each port is fluidly connected to one of the at least threelumina of the inner catheter.

Statement 11: The catheter system of Statement 1, wherein the outersheath further comprises at least three lumina extending from theproximal end to the distal end of the outer sheath.

Statement 12: The catheter system of Statement 11, wherein the outersheath comprises an inflation lumen, a suction lumen, and a catheterlumen, and wherein the inner catheter is positioned within the catheterlumen of the outer sheath.

Statement 13: The catheter system of Statement 12, wherein the outersheath further comprises a manifold at its proximal end comprising asuction port, a balloon inflation port, and a device access port,wherein each port is fluidly connected to one of the at least therelumina of the outer sheath.

Statement 14: The catheter system of Statement 12, wherein the catheterlumen is concentric with the suction lumen.

Statement 15: The catheter system of Statement 1 further comprising anagitator operable to agitate the thrombus.

Statement 16: The catheter system of Statement 15, wherein the outersheath further encloses the agitator.

Statement 17: The catheter system of Statement 15, wherein the agitatoris rail mounted on the outer sheath.

Statement 18: The catheter system of Statement 15, wherein the agitatorcomprises a plurality of protrusions.

Statement 19: The catheter system of Statement 15, wherein the agitatoris configured to protrude from the distal end of the outer sheath.

Statement 20: The catheter system of Statement 15, wherein the agitatoris operable to advance and retract over a catheter lumen of the outersheath.

Statement 21: The catheter system of Statement 15, wherein the agitatoris operable to be used without touching a wall of the vessel.

Statement 22: The catheter system of Statement 15, wherein the agitatorhas a pitch angle operable to reduce shear stress on the vessel duringoperation of the agitator.

Statement 23: The catheter system of Statement 15, wherein the agitatoris brush-like and is operable to clear the thrombus while alleviatingradial stresses on the vessel inner wall.

Statement 24: The catheter of claim 15, wherein the protrusions orplurality of protrusions are distributed helically along the length ofthe agitator.

Statement 25: A catheter for removal of a thrombus from a vessel,comprising: a catheter body having a proximal end and a distal end, thecatheter comprising: an encapsulation balloon at the distal end; and anagitator extending from the distal end, beyond the encapsulationballoon.

Statement 26: The catheter of Statement 25, wherein the agitator isoperable to not touch a wall of the vessel.

Statement 27: The catheter of Statement 25, wherein the encapsulationballoon is a compliant balloon operable to accommodate varying vesselsizes and minimize damage to the vessel.

Statement 28: A method of removing a thrombus in a patient in needthereof, the method comprising: inserting the catheter system of claim 1to a treatment area of a vessel; inflating the distal encapsulationballoon through an inflation lumen of the inner catheter; inflating theproximal encapsulation balloon through an inflation lumen of the outersheath; mechanically lysing the thrombus with an agitator; infusing aninfusion solution to the treatment area through the at least oneinfusion fenestration; applying negative suction to the treatment areathrough a suction lumen of the outer sheath, wherein there isisovolumetric suction and restoration of fluid within a thrombolytictreatment area between the distal encapsulation balloon and the proximalencapsulation balloon; and removing the catheter system from thepatient.

Statement 29: The method of Statement 28, wherein the infusion solutionis a thrombolytic solution, saline, or combinations thereof.

Statement 30: The method of Statement 29, wherein the thrombolyticsolution comprises tPA.

Statement 31: The method of Statement 28, wherein the negative suctionis applied for about 1 to about 30 minutes.

Statement 32: The method of Statement 28, wherein mechanically lysingthe thrombus comprises advancing and retracting the agitator over acatheter lumen of the outer sheath.

Statement 33: The method of Statement 28, wherein greater than about 90%luminal patency of the treatment area is restored.

Statement 34: The method of Statement 28, further comprising advancingthe catheter system from a femoral vein cannulation or an internaljugular vein cannulation, wherein a pulmonary embolism is treated withinthe patient.

What is claimed is:
 1. A catheter system for removal of a thrombus froma vessel, comprising: an inner catheter having a proximal end, aninfusion segment, and a distal end, the inner catheter comprising: atleast one infusion fenestration along the infusion segment; and a distalencapsulation balloon at the distal end; and an outer sheath having aproximal end and a distal end, the outer sheath comprising: a proximalencapsulation balloon at the distal end, wherein the outer sheathsurrounds at least a portion of the inner catheter and the distalencapsulation balloon and the proximal encapsulation balloon areseparated by a distance along the infusion segment.
 2. The cathetersystem of claim 1, wherein the distal encapsulation balloon and theproximal encapsulation balloon are compliant balloons operable toaccommodate varying vessel sizes and minimize damage or injury to thevessel.
 3. The catheter system of claim 1, wherein the distance betweenthe distal encapsulation balloon and the proximal encapsulation balloonis adjustable.
 4. The catheter system of claim 1, wherein the distancebetween the distal encapsulation balloon and the proximal encapsulationballoon form a thrombolytic treatment area, wherein the thrombus to beremoved is contained within the thrombolytic treatment area.
 5. Thecatheter system of claim 4, wherein the infusion segment is within thethrombolytic treatment area.
 6. The catheter system of claim 5, whereinthe inner catheter is operable to infuse a fluid to the thrombolytictreatment area and the outer sheath is operable to provide suction toremove fluid from the thrombolytic treatment area.
 7. The cathetersystem of claim 6, wherein the inner catheter and outer sheath areoperable to provide isovolumetric suction and restoration of fluidwithin the thrombolytic treatment area.
 8. The catheter system of claim1, wherein the inner catheter further comprises at least three luminaextending from the proximal end to the distal end of the inner catheter.9. The catheter system of claim 8, wherein the inner catheter comprisesan inflation lumen, a guide wire lumen, and an infusion lumen, andwherein at least one infusion fenestration along the infusion segment isconnected to the infusion lumen to enable infusion of fluid.
 10. Thecatheter system of claim 9, wherein the inner catheter further comprisesa manifold at its proximal end comprising an infusion port, a ballooninflation port, and a guidewire access port, wherein each port isfluidly connected to one of the at least three lumina of the innercatheter.
 11. The catheter system of claim 1, wherein the outer sheathfurther comprises at least three lumina extending from the proximal endto the distal end of the outer sheath.
 12. The catheter system of claim11, wherein the outer sheath comprises an inflation lumen, a suctionlumen, and a catheter lumen, and wherein the inner catheter ispositioned within the catheter lumen of the outer sheath.
 13. Thecatheter system of claim 12, wherein the outer sheath further comprisesa manifold at its proximal end comprising a suction port, a ballooninflation port, and a device access port, wherein each port is fluidlyconnected to one of the at least there lumina of the outer sheath. 14.The catheter system of claim 12, wherein the catheter lumen isconcentric with the suction lumen.
 15. The catheter system of claim 1,further comprising an agitator operable to agitate the thrombus.
 16. Thecatheter system of claim 15, wherein the outer heath encloses theagitator.
 17. The catheter system of claim 15, wherein the agitator israil mounted on the outer sheath, configured to protrude from the distalend of the outer sheath, and/or the agitator is operable to advance andretract over a catheter lumen of the outer sheath.
 18. The cathetersystem of claim 15, wherein the agitator is operable to be used withouttouching a wall of the vessel.
 19. The catheter system of claim 15,wherein the agitator comprises a plurality of protrusions or brushes ata pitch angle operable to reduce shear stress on the vessel.
 20. Thecatheter system of claim 19, wherein the plurality of protrusions aredistributed helically along the length of the agitator.